Alveolar macrophages have two major functions: (1) phaocytic function for removal of foreign materias and infectious agents. (2) secretion of substances by which macrophages interact with other cells, such as lymphocytes and fibroblasts. Recent investigations have shown that peritoneal macrophages secrete prostaglandins during phagocytosis and suggest that these substanes may play a role as mediators for the interaction between macrophages and lymphocytes. The principal objectives of this proposal are: (1) to determine whether prostaglandins are secreted by pulmonary macrophages and to identify the various types that are produced, (2) to examine their relationship to phagocytosis and (3) to study their roles in interactions between macrophages and other cells of the immune system, in both physiological and pathological conditions. 14C-arachidonic acid, a prostaglandin precursor, will be used to prelabel the phospholipid pool of cultured rabbit alveolar macrophages. By utilizing radiochemical, chromatographic and bioassay techniques, we will be able to identify the various prostaglandins produced by the macrophages, assess the activity of phospholipase A, and determine the source of dacylation for prostaglandin synthesis. The nature of the phagocytic stimulus to prostaglandin production will be studied using different types of phagocytic loads and inhibitors. Thus the specific step in the phagocytic process associated with prostaglandin release can be determined. The role of prostaglandins in the interaction between macrophages and lymphocytes will also be investigated by using conventional immunological techniques such as lymphoblast transformation, radioactive thymidine incorporation, migration inhibition factor assay and mixed lymphocyte culture.